The most important component of gene therapy in humans is the choice of an efficient and safe gene delivery system, otherwise known as vectors. Adeno-associated virus (AAV) based vectors have emerged as important tools for this purpose. However limitations, most notably, the immunological barriers related to the recipient and the virus coat protein preclude the universal application of this promising vector system. Unraveling how host cells perceive the viral intrusion and their immediate and long-lived response to this infection process is thus crucial. Our laboratory's research interests traverse and investigate aspects of the virus-host life cycle, dissect the tug-of-war initiated between these players to establish primacy and dwell on how it is possible to alter this milieu in favor of the virus. The information thus gathered is then used to bioengineer the vectors and develop improved gene delivery strategies. Such a multi-pronged basic biology approach to develop efficient vectors and their subsequent validation in pre-clinical models augurs well for their translation to human gene therapy.